IL-7 receptor is expressed on adult pre-B-cell acute lymphoblastic leukemia and other B-cell derived neoplasms and correlates with expression of proliferation and survival markers

Cytokine. 2010 Apr;50(1):58-68. doi: 10.1016/j.cyto.2009.12.001. Epub 2010 Jan 8.

Abstract

The interleukin (IL)-7 receptor (IL-7R) is expressed on human pre-B but not mature B-cells. We hypothesised that aberrant expression of IL-7R contributes to B-cell oncogenesis. Surface expression of IL-7R components CD127 and CD132, and intracellular Ki-67 and Bcl-2 were examined by flow cytometry on peripheral blood or bone marrow mononuclear cells (PBMC; BMMC) from patients with B-cell derived neoplasms, chronic human immunodeficiency virus type-1 (HIV-1) infection alone, or healthy volunteers. Plasma IL-7, IL-2, IL-4, IL-6, IL-10, IL-21, TNF-alpha, IFN-gamma and BAFF were measured by enzyme-linked immuno-sorbent assay or bead array. The effects of exogenous IL-7 on PBMC and BMMC were examined. CD127 expression was elevated in pre-B-cell acute lymphoblastic leukemia (pre-B-ALL) and in some cases of Non-Hodgkin's Lymphoma (B-NHL). Plasma IL-7 levels were higher in pre-B-ALL, B-cell chronic lymphocytic leukemia (B-CLL) and HIV-1 associated B-NHL (HIV-B-NHL) compared with control groups. CD127+ pre-B-ALL cells had higher expression of Ki-67, Bcl-2 and CD132 than CD127- counterparts. Unlike T-lineage cells, CD127+ pre-B-ALL cells did not down-regulate CD127 in response to exogenous IL-7. Patients with B-cell derived neoplasms had elevated circulating IL-10 and decreased BAFF. These findings support a role for the IL-7/IL-7R system in B-cell oncogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor / blood
  • Biomarkers, Tumor / metabolism*
  • Cell Differentiation
  • Cell Membrane / metabolism
  • Cell Proliferation
  • Cryopreservation
  • Cytokines / blood
  • Female
  • Flow Cytometry
  • Humans
  • Interleukin Receptor Common gamma Subunit / metabolism
  • Ki-67 Antigen / metabolism
  • Male
  • Middle Aged
  • Phenotype
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / blood
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / metabolism*
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / pathology*
  • Prospective Studies
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Receptors, Interleukin-7 / immunology*
  • Retrospective Studies
  • Survival Analysis
  • T-Lymphocytes / pathology

Substances

  • Biomarkers, Tumor
  • Cytokines
  • IL2RG protein, human
  • Interleukin Receptor Common gamma Subunit
  • Ki-67 Antigen
  • Proto-Oncogene Proteins c-bcl-2
  • Receptors, Interleukin-7